Given that everything is very individual in nature, how can a biologist come up with general statements about how life functions? The answers can only be found using models that represent the entire whole. Modern research uses representative species from the kingdom of bacteria, fungi, plants and animals to glean information about fundamental biological principles. How can the knowledge gained be transferred to other organisms, including humans? And what is it that makes yeasts, worms, fruit flies and other organisms such excellent experimental models?
Life consists of cells. All cells consist of DNA; they divide, breathe and communicate. The basic functions have remained astonishingly conserved during evolution. Genomic research is revealing to a growing extent that individual molecular constituents have also repeatedly been used during evolution. In many cases, it is possible to achieve insights into how proteins are transported in our own body cells when looking at the protein transport mechanisms in yeasts and fruit flies, for example. Experiments involving sepia or rats provide us with information on how the human neurons function. This might even pave the way for the development of methods for the treatment of diseases. The nutrition industry is one area that can make use of biological processes. Researchers are using model organisms for their research in all areas of biology. These organisms help the researchers to come to well-founded conclusions about humans without requiring experiments to be carried out on actual human beings.
Not all organisms are equally well suited as experimental models. What is most important for scientists is that the experimental subjects can be easily handled and bred in the laboratory. For example, the bacterium Escherichia coli is easy to cultivate; it divides every twenty minutes and does not run away when placed under the microscope. Since it is not pathogenic and has a relatively small genome (about 4.6 million base pairs), E. coli became one of the most important model organisms for genetic studies on bacteria from around 1950. It is simple to create a large number of bacterial mutants within a short time, which enables researchers to investigate the function of genes. Findings obtained with E. coli have made a considerable contribution to providing us with greater insights into human genetics. For example, the mechanism of DNA replication is very similar in bacteria and eukaryotic cells (i.e. cells with a true nucleus). It is far easier to genetically modify a bacterial cell than a human one, which has a far more complicated structure. Many experimental methods have been developed for E. coli. These methods are still used today and make these bacteria an excellent study object for the investigation of basic molecular genetic mechanisms.
The differences between bacteria and animal cells nevertheless limit the general informative value of such experiments. This is why scientists prefer to use model organisms that are more similar to humans. However, easy handling still remains a crucial issue when choosing a model organism. The yeast Saccharomyces cerevisiae fulfils both the aforementioned requirements: it is a unicellular fungus that can be easily cultivated in the laboratory. It also divides quickly, as is the case with E. coli, and has a relatively small genome. In addition to these criteria, it is far more similar to animal, plant or human cells than bacterial cells are. Like all eukaryotic cells, Saccharomyces has cellular organelles and chromosomes and underlies a molecular control mechanism that regulates DNA replication and cell division. Scientists were able to clarify the basic mechanisms of the cell cycle using Saccharomyces.
From multicellular organisms to humans
Drosophila melanogaster, which is commonly known as fruit fly, also has a short generation time. The Drosophila genome is also very small and has only about 140 million base pairs. These two aspects make fruit flies excellent experimental objects for studies in genetics. In addition, fruit flies are multicellular organisms with different tissues and a nervous system, and hence more similar to humans than yeast. Between 1910 and the 1950s, Drosophila was used by famous geneticists such as Thomas Hunt Morgen to clarify the basic principles of inheritance. Over the last few years, Drosophila has also been used to study aspects of neurobiology or embryonic development. The threadworm Caenorhabditis elegans is another popular experimental organism, particularly amongst developmental biologists, due to the identical number of cells in adult threadworms (cell number constancy). Adult hermaphrodites always have 959 cells, adult males 1031 cells. The origin of the cells can be accurately followed from the fertilised egg cell. Transparent threadworms are excellently suited for the study of the mechanisms of programmed cell death (apoptosis), which is why they play an important role in ageing research.
Besides fruit flies and C. elegans, many developmental biologists use zebra fish (Danio rerio) for their research. Evolutionary biologists like to use African cichlids for their studies, as they comprise many different species, just like the Darwin finches. Agriculture and plant research, which is highly important for the pharmaceutical industry, also have special model organisms. The best known example is the thale cress (Arabidopsis thaliana) which can easily be grown in the laboratory, is easy to genetically modify and is thus very useful for studies in molecular, developmental and cell biology. The inconspicuous weed is of great importance for plant geneticists. Plant biologists investigating phylogenetic aspects such as the evolution of plants prefer to use prehistoric organisms such as the moss Physcomitrella patens or green algae, which are relatives of bacteria. These model organisms are a lot simpler than the evolutionarily younger flowering plants. However, they already possess many plant characteristics such as the ability to carry out photosynthesis or employ a range of different strategies to cope with stress stimuli such as UV radiation or high salt concentrations.
The limits of similarity
Animals such as rats, mice and sometimes also pigs are particularly suitable for the development of drugs or for immunological research. Like people, these mammals have an immune system and a high percentage of identical gene sequences. Biomedical specialists refer to certain animal species or lines, which spontaneously or after specific treatment develop certain diseases, as animal models. Using such animal models, researchers hope to obtain insights into the causes and treatment of human diseases. However, it is often difficult to transfer the results obtained in animal experiments to the situation in humans. Drugs that might be beneficial for mice or rats, might not be tolerated by the human organism. Despite the huge similarity of the basic blueprints between the aforementioned model organisms and humans, as well as the huge similarity of the basic biological processes, animal experiments can only provide indications as to the potential adverse effects of drugs. Human studies are indispensable in medicine. In addition, insights into the biological processes obtained with model organisms in basic research do not allow the 100% transfer of the information gained to other organisms. In future, comparative studies involving different species will become more and more important.
The future of research
The gene sequences of almost all model organisms have now been deciphered. This not only enables the comparison of different groups of organisms, which helps to clarify the function of genes more quickly. In addition, systemic approaches also enable researchers to investigate entire gene networks. No organism with an unknown genome is likely to become a model organism in modern research. However, it is becoming easier and cheaper to decipher a genome sequence. As research areas expand and become more and more specialised, the number of model organisms will also increase. For example, microbiologists investigating the ability of bacteria to remove toxic substances from cropping soil, cannot use the intestinal E. coli bacteria, but have to resort to soil-dwelling bacterial specialists.
The situation is similar for scientists investigating the human hepatitis B virus (HBV). HBV normally only infects apes and humans, neither of which can be used in experiments for ethical reasons. The exotic tree shrews (Tupaia) are a solution to this problem since they are the only known animals outside of the hominids that can serve as hosts for viruses. It is for this particular reason that Tupaia might well become a model organism in the future. This example is a perfect illustration of the fact that it is not only conventions, but often also the scientific problem that determines which organism is particularly suitable as a study object.
mn – 24.08.09
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Burke, H. Judd: Experimental Organisms Used in Genetics; ENCYCLOPEDIA OF LIFE SCIENCES © 2001, John Wiley & Sons, Ltd.
Alberts, Johnson, Lewis, Raff, Roberts, Walter: Molekularbiologie der Zelle; 4. edition 2004; WILEY-VCH Verlag GmbH & Co. KgaA, Weinheim